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Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells

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Abstract

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1–4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1–4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1–4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1–4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1–4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1–4 and cisplatin could induce p53. All complexes 1–4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.

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Acknowledgements

This work was funded by the University of Jeddah, Jeddah, Saudi Arabia, under grant No. (UJ-23-DR-130). Therefore, the authors thank the University of Jeddah for its technical and financial support.

Funding

This project was funded by the University of Jeddah, Jeddah, Saudi Arabia, under grant No. (UJ-23-DR-130). Therefore, the authors thank the University of Jeddah for its technical and financial support.

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Authors and Affiliations

  1. Department of Chemistry, College of Science, University of Jeddah, 21959, Jeddah, Saudi Arabia

    Mohamed M. El-bendary, Abdullah Akhdhar, Abdullah S. Al-Bogami & Doaa Domyati

  2. Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt

    Mohamed M. El-bendary

  3. Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia

    Abdulaziz A. Kalantan, Samer M. Alamoudi, Ryan A. Sheikh & Ehab M. M. Ali

  4. Department of Chemistry, College of Sciences & Arts, King Abdulaziz University, 21911, Rabigh, Saudi Arabia

    Faisal Ay Alzahrani

  5. Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt

    Ehab M. M. Ali

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  1. Mohamed M. El-bendary
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Contributions

MME: Conceptualization. MME and AA: Data curation. MME, EMMA and ASA: Formal analysis. DD: Funding acquisition. MME and TSS: Investigation. MMA, EMMA: Methodology. MME: Project administration. AAK and FA: Resources. SA and RS: Software. MME, AA: Supervision. MME, AA and EMMA: Visualization. MME: Writing–original draft. MME, EMMA and AA: Writing–review & editing.

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El-bendary, M.M., Akhdhar, A., Al-Bogami, A.S. et al. Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells. Biometals (2024). https://doi.org/10.1007/s10534-023-00580-z

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